Dynamics of pharmaceutical amorphous solids: the study of enthalpy relaxation by isothermal microcalorimetry.
Dynamics of pharmaceutical amorphous solids: the study of enthalpy relaxation by isothermal microcalorimetry.
复制标题
药物无定形固体的动力学：等温微量热法的焓弛豫研究。
DOI：
10.1002/jps.10181
复制
发表时间：
2002
影响因子：
3.8
通讯作者：
M. Pikal
中科院分区：
文献类型：
--
作者：
Jinsong Liu;D. Rigsbee;C. Stotz;M. Pikal
结构弛豫时间是焓弛豫中涉及的分子迁移率的量度，因此是确定药物在无定形制剂中的物理化学性质和反应性的无定形（玻璃状）药物固体的动力学的量度。在这篇文章中，我们描述了一种新的方法，使用等温微量热法，它直接测量的热释放速率在松弛过程中的结构松弛的表征。然后从功率数据到Kohlrausch-Williams-Watts（KWW）方程的导数版本的拟合获得结构弛豫时间。使用等温微量热计，热活性监测器（TAM）的弛豫时间的淬火和冻干样品的EQUIPMENT进行了研究。除了KWW导函数外，还采用修正的拉伸指数函数（MSE）的导数方程来评估TAM数据。后者（MSE）似乎有数值优势的KWW方程。数据表明，正如预期的那样，无定形固体的结构弛豫时间取决于一些变量，包括材料的性质，温度，水分含量，热历史等。等温微量热与TAM提供了一个非常快速和可靠的方式来表征玻璃材料的动态，这在许多方面是上级的传统DSC方法。在一定程度上的稳定性和结构弛豫动力学的玻璃是相关的，结构弛豫参数来自等温微量热法可以提供数据，用于合理开发稳定的肽和蛋白质制剂和控制它们的加工。
The structural relaxation time is a measure of the molecular mobility involved in enthalpy relaxation, and thus, is a measure of the dynamics of amorphous (glassy) pharmaceutical solids that determines physicochemical properties and reactivity of drugs in amorphous formulations. In this article we describe a novel method for characterization of structural relaxation using isothermal microcalorimetry, which directly measures the rate of heat release during the relaxation processes. The structural relaxation time is then obtained from a fit of the power data to the derivative version of the Kohlrausch-Williams-Watts (KWW) equation. The relaxation times of quenched and lyophilized samples of saccharides were studied using an isothermal microcalorimeter, the Thermal Activity Monitor (TAM). In addition to the KWW derivative function, a derivative equation of the modified stretched exponential function (MSE) was employed to evaluate TAM data. The later (MSE) appeared to have numerical advantages over the KWW equation. The data demonstrate, as expected, that structural relaxation times of amorphous solids depend on a number of variables, including nature of material, temperature, moisture content, thermal history, etc. Isothermal microcalorimetry with the TAM provides a very fast and reliable way to characterize the dynamics of glassy materials, which in many respects is superior to the conventional DSC approach. To the extent stability and structural relaxation dynamics in the glass are correlated, structural relaxation parameters derived by isothermal microcalorimetry may provide data useful for rational development of stable peptide and protein formulations and for the control of their processing.